P28 EFFICACY AND SAFETY OF CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN PATIENTS WITH PROGRESSIVE MULTIPLE MYELOMA (MM) AFTER EXPOSURE TO NON-CELLULAR ANTI-B-CELL MATURATION ANTIGEN (BCMA) IMMUNOTHERAPY
Authors: N. van de Donk, M.-V. Mateos, Y.C. Cohen, P. Rodriguez-Otero, B. Paiva, A.D. Cohen, T. Martin, A. Suvannasankha, D. Madduri, C. Corsale, J.M. Schecter, K.C. De Braganca, C.C. Jackson, H. Varsos, W. Deraedt, T. Roccia, P. Mistry, X. Xu, K. Li, E. Zudaire, M. Akram, L. Pacaud, I. Avivi, J. San-Miguel
Journal: HemaSphere (2023)

Introduction: CARTITUDE-2 (NCT04133636) is a phase 2 study evaluating cilta-cel, an anti-BCMA CAR-T therapy, in several MM patient populations. We present updated data with longer follow-up on cohort C patients with previous exposure to a non-cellular anti-BCMA immunotherapy. Methods: Cohort C patients with progressive MM after treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent received a single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) 5–7 days post lymphodepletion. Primary endpoint: minimal residual disease (MRD) negativity at 10-5. Secondary endpoints: overall response rate (ORR), duration of response (DOR), and adverse events (AEs). Results: As of June 1, 2022, 20 patients received cilta-cel (13 ADC exposed; 7 BsAb exposed). 6 patients (30%) received anti-BCMA treatment as last line of therapy (LOT; n=4 ADC, n=2 BsAb). During prior anti-BCMA treatment, best responses included very good partial response (ADC group: 2 patients, BsAb group: 1 patient), stringent complete response (ADC group: 1 patient), and complete response (BsAb group: 1 patient); the rest had best response of stable disease or PD (1 patient was not evaluable). At baseline (median age: 62.5 years, male: 60%), 3 (15%) patients had high-risk cytogenetics (all del17p), and 5 (25%) had baseline extramedullary disease. Patients had a median of 8 prior LOT; triple-class refractory (n=18 [90%]), penta-drug refractory (n=11 [55%]), refractory to non-cellular anti-BCMA treatment (n=16 [80%]) (Fig 1A). Median time from last anti-BCMA agent to cilta-cel infusion was 195 days. At a median follow-up of 18.0 months, 7/10 evaluable patients (70%) were MRD-negative at 10-5 (ADC group [n=5/7 evaluable, 71.4%]; BsAb group [n=2/3 evaluable, 66.7%]). ORR was 60% for the full cohort, 61.5% in the ADC group, and 57.1% in the BsAb group (Fig 1B). Median DOR was 12.8 months in the full cohort, 12.8 months in the ADC group, and 8.2 months in the BsAb group. Median PFS was 9.1 months in the full cohort, 9.5 months in the ADC group, and 5.3 months in the BsAb group. Cilta-cel responders had a shorter median duration of last anti-BCMA agent exposure (29.5 days) compared with non-responders (63.5 days). Responders also had a longer median time from last anti-BCMA treatment exposure to apheresis (161.0 days) than non-responders (56.5 days). Most common AEs were hematologic. CRS occurred in 12 (60%) patients (all grade 1/2); median time to onset was 7.5 days and median duration was 6.0 days. ICANS occurred in 4 (20%) patients (2 grade 3/4); median time to onset was 9.0 days and median duration was 7.0 days. ICANS was recovered or resolved in 3 patients. No patient had movement or neurocognitive treatment emergent AEs/parkinsonism. 12 deaths occurred: 8 due to PD, 2 due to COVID-19 pneumonia (not treatment related), 1 due to subarachnoid hemorrhage (not treatment related), and 1 due to C. difficile colitis (treatment related). Conclusions: Heavily pretreated patients with MM and previous exposure to a non-cellular anti-BCMA therapy showed favorable responses following cilta-cel treatment. However, depth and DOR appear lower than that seen in anti-BCMA-naive patients treated with cilta-cel (median DOR was not reached in heavily pretreated but anti-BCMA naive CARTITUDE-1 patients at 27.7 months). These data may help inform treatment plans, including sequencing and washout period between BCMA-targeting agents.